Kidney Injury Molecule-1 Levels Research Articles

Analysis of plasma KIM-1 as a biomarker for recurrence risk after resection for localized renal cell carcinoma.

342 Background: Recurrence is common after nephrectomy for renal cell carcinoma (RCC), but no circulating biomarkers are available to identify patients at highest risk of recurrence who may benefit from adjuvant therapy. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Methods: Banked plasma samples were analyzed from the ECOG-ACRIN 2805 (ASSURE) trial evaluating adjuvant sunitinib, sorafenib, and placebo in resected high-risk RCC. KIM-1 levels were measured at trial enrollment 4-12 weeks post-nephrectomy (baseline) and on cycle 2 day 1 (C2D1) using a previously validated microbead assay. A lognormal accelerated failure time model was used to test for association between circulating KIM-1 and disease-free survival (DFS). Results: Plasma samples from 418 patients were analyzed. In univariable and multivariable analyses, higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms. This association remained independently significant after adjustment for Fuhrman grade, T-stage, N-stage, and tumor histology (survival time ratio 0.56 for 75th vs 25th percentile of KIM-1, 95% CI 0.42-0.73, p < 0.001). The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement. The addition of baseline KIM-1 improved the concordance of both the SSIGN and UISS prognostic models (SSIGN concordance 0.57 vs 0.43, p = 0.05; UISS concordance 0.60 vs 0.40, p = 0.0005). C2D1 KIM-1 was not an independent predictor for DFS after adjusting for baseline KIM-1. Conclusions: Elevated plasma KIM-1 level at post-nephrectomy baseline is associated with worse DFS in RCC. This is consistent with the hypothesis that post-nephrectomy plasma KIM-1 may be a biomarker for microscopic residual disease. The model was additionally adjusted for papillary and chromophobe histology, sex, and ECOG performance status. [Table: see text]

Desfechos em Pacientes com Fenômeno de No-Reflow Coronário e a Relação entre a Molécula-1 de Lesão Renal e o Fenômeno de No-Reflow Coronário

ResumoFundamento O fenômeno de no-reflow coronário (CNP, do inglês Coronary no-reflow phenomenon) está associado a um risco aumentado de eventos cardiovasculares adversos maiores (ECAM).Objetivo Este estudo teve como objetivo avaliar a relação entre os níveis séricos da Molécula-1 de lesão renal (KIM-1) e o CNP em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST).Métodos Este estudo incluiu um total de 160 pacientes (113 homens e 47 mulheres; média de idade: 61,65 ± 12,14 anos) com diagnóstico de IAMCSST. Os pacientes foram divididos em dois grupos, o grupo reflow (GR) (n = 140) e o grupo no-reflow (GNR) (n = 20). Os pacientes foram acompanhados durante um ano. Um valor de p<0,05 foi considerado significativo.Resultados O CNP foi observado em 12,50% dos pacientes. O nível de KIM-1 sérico foi significativamente maior no GNR do que no GR (20,26 ± 7,32 vs. 13,45 ± 6,40, p<0,001). O índice de massa corporal (IMC) foi significativamente maior no GNR do que no GR (29,41 (28,48-31,23) vs. 27,56 (25,44-31,03), p=0,047). A frequência cardíaca (FC) foi significativamente menor no GNR do que no GR (61,6 ± 8,04 vs. 80,37 ± 14,61, p<0,001). O escore do European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) foi significativamente maior no GNR do que no GR (3,06 ± 2,22 vs. 2,36 ± 2,85, p=0,016). A incidência de AVC foi significativamente maior no GNR do que no GR (15% vs. 2,90%, p=0,013). O nível basal de KIM-1 (OR = 1,19, IC 95%: 1,07-1,34, p=0,002) e HR (OR = 0,784, IC 95%: 0,69-0,88, p<0,001) foram os preditores independentes de CNP.Conclusão Em conclusão, os níveis séricos basais de KIM-1 e a FC mais baixa estão independentemente associados com CNP em pacientes com IAMCSST, e o acidente vascular cerebral foi significativamente maior no GNR em um ano de seguimento. (Arq Bras Cardiol. 2021; 116(2):238-247)

Predictive value of novel biomarkers for chronic kidney disease among workers occupationally exposed to silica.

There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers.

Clinical implication of kidney injury molecule (KIM-1) in blood plasma of renal-cell cancer patients

Background. The most important task in the field of renal-cell cancer (RCC) treatment results improvement is the search and validation of the markers for its early diagnostics still absent in the clinical practice. It was established that even before the onset and/or detection of RCC the level of kidney injury molecule-1 (KIM-1) in blood plasma did increase.Objective of the study — comparative evaluation of KIM-1 levels in blood plasma of practically healthy persons, RCC cancer, benign kidney tumor patients, patients with non-oncological renal pathologies, and analysis of its role in RCC diagnostics and prognosis.Materials and methods. 125 RCC (age 33—81 years), 14 — benign kidney neoplasms (29—84 years) patients, 90patients with chronic nephritis (28—82 years) and 68 practically healthy persons (18—71 years) were included in the study. Plasma KIM-1 content was measured using Human Serum TIM-1/KIM-1/HAVCR Quantikine® ELISA kit (R&amp;D Systems Biotechne®, USA).Results. KIM-1 level in blood plasma of RCC and chronic nephritis patients was significantly higher than in control (medians 305, 282 and 37.8pg/ml respectively, p &lt;0.0001). The rate of KIM-1 elevation over cut-offvalue 90pg/ml corresponding to the upper 95 % confidence interval of control in RCC patients comprised 79.2 %, in patients with nephritis — 83 %, in those with benign renal tumors — 50 %. Specificity in relation to healthy control was 96 %. KIM-1 level highly significantly increased with RCC progression, and already at stage I was 4.3-fold higher by median than in control (p &lt;0.0001). Sensitivity of stage I—IIRCC detection at cut-off 90pg/ml comprised 75 %; stage III—IV — 94 %. The highest plasma KIM-1 levels were detected in papillary cancer patients (median 644pg/ml), that was more than 2-fold higher than in clear-cell and 32-fold higher than in chromophobic RCC. Plasma KIM-1 median level was 7-fold higher in patients with G3 4RCC than in those with G12 (p &lt;0.0001). At the cut-off KIM-1 value of 163pg/ml, corresponding to the median at stage I, significant differences in 3.5-years overall survival both in the total group: 49 % at high, 95 % at low marker level (p &lt;0.01), and at stage I RCC: 62 % and 100 % respectively (p &lt;0.05) — were revealed.Conclusion. Plasma KIM-1 may become the first highly sensitive marker for the early detection of RCC, but it does not allow differentiating between oncologic and non-oncologic renal pathologies. Increased basal plasma KIM-1 is an unfavorable prognostic factor irrespective of the stage of tumor progression.

Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults

BackgroundRecent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown.MethodsFrom February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test.ResultsThe 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36).ConclusionsIn this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline.Trial registrationClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

Hepato-renal toxicities associated with heavy metal contamination of water sources among residents of an oil contaminated area in Nigeria

ObjectivesThis study was conducted to estimate the heavy metal (HM) content of water sources from oil contaminated area, HM and hepato-renal functions of residents and to determine association between consumption of crude oil contaminated water and development of multiple organ toxicities. MethodsHeavy metals (Pb, Cd, As, Hg) content of 20 surface water sources (SWS) and 20 underground water sources (UWS) from crude oil contaminated area and 40 water sources (20 SWS and 20 UWS) from uncontaminated area (controls) were estimated using AAS. The HM, indices of liver function (aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total protein (TP), albumin, total and conjugated bilirubin (TB and CB)) and renal functions (urea, creatinine, sodium, chloride, potassium, bicarbonate and kidney injury molecule-1 (KIM-1)) were determined in 120 residents each from contaminated and control areas using enzyme-colorimetry and ELISA methods. ResultsThe HM levels of all water sources studied were above WHO standards. Water sources from contaminated area had higher HM levels compared to control. HM contents of SWS from contaminated area and control were higher than UWS from both areas. Residents of contaminated area had higher levels of HM, urea, bicarbonate, chloride, sodium, KIM-1, ALP, GGT, AST, ALT, TB and CB and lower TP and albumin compared to residents of control area. ConclusionWater contamination with crude oil is associated with elevated HM content with perturbations in HM, liver and renal functions of consumers which may suggest an increased risk of hepato-renal toxicities.

Prediction of acute renal allograft rejection by combined HLA-G 14-bp insertion/deletion genotype analysis and detection of kidney injury molecule-1 and osteopontin in the peripheral blood

IntroductionAcute renal rejection usually fails to be diagnosed before the increase in the serum creatinine levels, and the resultant damage to the renal tissues occur in varying degrees. We hypothesized that the combined detection of human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion genotypes and kidney injury molecule-1 (KIM-1) and osteopontin (OPN) levels in serum might facilitate the prediction of acute renal allograft rejections in kidney transplant recipients. MethodsHLA-G 14-bp insertion/deletion genotypes and the serum KIM-1 and OPN levels of 77 kidney transplant recipients were determined and compared before operation and on days 1, 4, and 7 after the operation (32 in acute rejection [AR] group and 45 in stable allograft function [STA] group). These 3 indicators were combined to establish a model for the early prediction of AR. ResultsThe KIM-1 levels in the serum of patients were significantly higher in the AR group than in the STA group. The area under the receiver operator characteristics (ROC) curve (AUC) of KIM-1 for the prediction of rejection was maximized on the1st day after operation, with a sensitivity of 84.4% and a specificity of 86.7%. The OPN levels in the serum of patients were significantly higher in the AR group than in the STA group only before operation and on the 7th day after operation. The AUC of OPN for the prediction of rejection was maximized on 7th day after operation, with a sensitivity of 68.8% and a specificity of 88.9%. The HLA-G + 14-bp allele frequency was also significantly higher in the AR group than in the STA group. The results of these three indicators were converted into a qualitative method. If any two of the three indicators show as positive, it was diagnosed as acute rejection, and it has the highest ability to predict acute rejection with a sensitivity and specificity of 84.38% and 91.11%, respectively. ConclusionsThe HLA-G 14-bp insertion/deletion genotype and KIM-1 and OPN levels in the patients' serum were significantly different between the AR and STA groups. The power of predicting acute renal allograft rejection could be improved by combined these three biomarkers.

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. The current research aimed at evaluating the GA effect on CP-related renal toxicity. In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue. CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

Urine NGAL and KIM-1-Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study.

The deterioration of renal function after childhood solid tumors treatment is the result of using the intensive multimodal therapy. In recent years, urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers of early kidney damage. The aim of the present study was to determine whether anticancer treatment has any effect on the concentration of KIM-1 and NGAL and its association with renal impairment in survivors of childhood solid tumors. Sixty patients previously treated for solid tumors were involved in this study. The median time after end of treatment was 8.35 years. Urine KIM-1 and NGAL levels were measured using immunoenzymatic ELISA commercial kits. Higher levels of urine NGAL, KIM-1/cr. (creatinine), and NGAL/cr. ratios were found in comparison with healthy controls (p < 0.0001). Among all subjects, 23% were found to have decreased estimated glomerular filtration rate (eGFR). A strong correlation between KIM-1/cr. and a cumulative dose of ifosfamide was observed (r = 0.865, p < 0.05). In addition, a moderate correlation between NGAL/cr. and a cumulative dose of cisplatin was identified (r = 0.534, p < 0.05). The AUC for KIM-1/cr. was 0.52, whereas NGAL/cr. showed a diagnostic profile describing the AUC of 0.67. Univariable regression showed significant associations between NGAL/cr. ratio and subjects after unilateral nephrectomy (coeff. 63.8, p = 0.007), cumulative dose of cisplatin (coeff. 0.111, p = 0.033), and age at diagnosis (coeff. 3.75, p = 0.023). The multivariable model demonstrated only cumulative dose of cisplatin as an independent factor influence on NGAL/cr. ratio. The results of our study showed increased levels of urine KIM-1 and NGAL many years after completion of the childhood solid tumors treatment, which correlated positively with a cumulative dose of ifosfamide and cisplatin. This study also suggests that unilateral nephrectomy could affect the concentration of the studied biomarkers.

The creation of unilateral intermittent and unintermittent renal ischemia-reperfusion models in rats.

Background and Aim:This study aims to establish unilateral intermittent and unintermittent partial nephrectomy-like renal ischemia-reperfusion (I-R) model in rats and to compare the results with biochemical findings.Material and Methods:The study was conducted on 24 adult 8-week-old male Wistar-Albino rats, each weighing s200–250 g. The rats were divided into three groups. In the Sham group (n = 8), the kidney was surgically exposed and closed. We designed experimental I-R models in the second group (n = 8, a total of 30-min ischemia model in the manner of 3 intermittent sets 8 minutes clamping and 2 min unclamping) and in the third group (n = 8, one session of 30-min unintermittent ischemia). In postoperative day 1, the rats were sacrificed, and the effects of I-R models on the renal tissue were comparatively assessed by evaluating serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum kidney injury molecule-1 (KIM-1), urinary NGAL, urinary KIM-1, and serum creatinine levels.Results:Urinary NGAL and KIM-1 levels were significantly higher in the continuous ischemia group when compared to those in the sham and intermittent ischemia groups (P < 0.05). In the intermittent ischemia group, urinary NGAL and urinary KIM-1 levels were significantly higher than those in the sham group (P < 0.05). Although the results of serum NGAL, serum KIM-1, and serum creatinine levels seemed to be in parallel to the results of urinary markers, no statistically significant difference was found.Conclusion:Renal injury was significantly less in the intermittent I-R model when compared to that in the unintermittent I-R model in our experimental rat study.

The Diagnostic Value of Combined Detection of Kidney Injury Molecule-1 and Urine Microsomal Protein in Early Stage Nephropathy of Gestational Hypertension

To investigate the diagnostic value of urine kidney injury molecule-1 and urine microsomal protein combined test in early stage nephropathy of gestational hypertension. 72 patients with gestational hypertension treated at the hospital from December 2018 to December 2019 were randomly selected as subjects and 72 normal pregnant women who gave birth at the hospital during the same period were randomly selected as controls. Urinary microsomal protein levels were measured by immune enhanced turbidimetric assay, while urinary kidney injury molecule-1 levels were measured by enzyme linked immunosorbent assay. Blood urea nitrogen, high-sensitivity C-reactive protein levels, and specificity and sensitivity of urine kidney injury molecule-1 and urine microsomal serum proteins in the two groups and their subgroups were analyzed comparatively. The levels of urinary kidney injury molecule-1 and urinary microsomal serum protein were higher in the study group than in the control group. Among the three subgroups of the study group, urinary kidney injury molecule-1 and urinary microsomal serum protein levels were significantly increased in the mid and late pregnancy groups compared to the early pregnancy group. In the subgroup with impaired renal function, the urinary kidney injury molecule-1 and urinary microalbumin levels were significantly higher than those in the subgroup with normal renal function and the difference was statistically significant (p<0.05). In terms of blood urea nitrogen and high-sensitivity C-reactive protein levels, blood urea nitrogen and high-sensitivity C-reactive protein levels in the study group were higher than those in the healthy control group and estimated glomerular filtration rate was lower than those in the healthy control group. Urinary kidney injury molecule-1 level and urinary microsomal protein in the study group showed positive correlation with blood urea nitrogen and high-sensitivity C-reactive protein (both p<0.05), and negative correlation with Estimated glomerular filtration rate. In terms of sensitivity and specificity, the results showed that the specificity and sensitivity of the combined test were significantly higher than that of the individual test and the difference was statistically significant (p<0.05). The detection of serum kidney injury molecule-1 and microsomal protein and other indicators to determine the degree of early renal impairment in pregnancy induced hypertension is beneficial for early clinical treatment and is of great clinical significance for pregnant women and pregnancy outcomes.

Biomarkers of acute kidney injury in patients with nephrotic syndrome.

ABSTRACTIntroduction:Emergence of acute kidney injury (AKI) in patients with nephrotic syndrome (NS) requires prompt diagnosis and differentiation between acute tubular necrosis (ATN) and proliferative glomerulonephritis. We studied the potential use of commercial urinary biomarkers' tests in the diagnosis of AKI in patients with NS.Methods:A cross sectional estimate of urinary concentrations of KIM-1 and NGAL was performed in 40 patients with NS: 9 with proliferative glomerulopathy, being 4 with AKI and 31 without proliferative glomerulopathy, being 15 with AKI. AKI was defined using the KDIGO criteria.Results:The mean age was 35 ± 16 years. The main diagnoses were focal and segmental glomerulosclerosis (10, 25%), membranous glomerulopathy (10, 25%), minimal change disease (7, 18%), lupus nephritis (6, 15%), and proliferative glomerulonephritis (3, 8%). Patients with ATN had higher levels of urinary KIM-1 (P = 0.0157) and NGAL (P = 0.023) than patients without ATN. The urinary concentrations of KIM-1 (P= 0.009) and NGAL (P= 0.002) were higher in patients with AKI than in patients without AKI. Urinary NGAL and KIM-1 levels were significantly higher in patients with ATN without proliferative glomerulonephritis than in patients with proliferative glomerulonephritis (P = 0.003 and P=0.024, respectively).Conclusions:Neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) estimates correlated with histological signs of ATN and were able to discriminate patients with AKI even in conditions of NS. Furthermore, urinary levels of NGAL and KIM-1 may be useful in the differential diagnosis of acute tubular necrosis and exudative glomerulonephritis in patients with nephrotic syndrome.

Urinary Kidney Injury Molecule-1 as an Early Detection Biomarker for Diagnosis of Acute Kidney Injury in Patients of Snake Bite

Introduction: Acute Kidney Injury (AKI) refers to a sudden impairment of kidney function that results in the retention of nitrogenous waste products. Acute tubular necrosis involves localised necrosis of epithelial lining in renal tubules. A soluble form of human Kidney Injury Molecule-1 (KIM-1) is a type 1 membrane-spanning protein which lends epithelial cells the capacity to perceive and phagocytose dead cells in post ischaemic kidney. Aim: To estimate urinary KIM-1 level in patients with snake bite as a potential biomarker for early detection for AKI. Materials and Methods: This was an analytical case-control study, which was conducted on 100 patients admitted for snake bite at Thanjavur Medical College and hospital, Thanjavur, Tamil Nadu, India, from January 2014 to August 2014. Patients without AKI were regarded as controls and those who developed AKI were considered as cases. Blood and urine samples were collected and analysed for urinary KIM-1 by Enzyme-Linked Immunosorbent Assay (ELISA), method, serum creatinine (by kinetic JAFFE’S method) and serum urea (by Urease- glutamate dehydrogenase method). Student’s t-test was used and p-value &lt;0.05 was regarded significant. Pearson’s correlation coefficient was used to assess correlation between measured parameters. Results: Among 100 patients, 44 were diagnosed as patients having AKI and 56 of them did not develop AKI. No significant difference was found in urinary KIM-1 values between age group of &lt;40 years and age group ≥40 years in cases (p-value=0.39) and in controls (p-value=0.65). A significant elevation of urinary KIM-1 was seen among cases of snake bite who developed AKI. Urinary KIM-1 levels were found to significantly rise within 24 hours of admission (p-value &lt;0.001), whereas, serum creatinine and urea values were not increased until the day 3 of nephrotoxic trauma. The urine KIM-1 and serum creatinine on day 1 had negligible correlation (r-value=0.093, p-value=0.54) and urine KIM-1 and urea on day 1 had low positive correlation (r-value=0.380, p-value=0.011). With progressive damage to the kidneys, a positive correlation was found between urine KIM-1 and serum urea (r-value=0.864), creatinine (r-value=0.882) on third day. Also, levels of urinary KIM-1 significantly increased (p&lt;0.001) with the severity of tubular injury. Conclusion: Urinary KIM-1 is a promising quick predictive marker of AKI in contrast to traditional markers, serum urea and creatinine.

A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of High-Dose, Short-Term Vitamin D Administration in the Prevention of Acute Kidney Injury after Cardiac Surgery

Background: Acute kidney injury (AKI) after cardiac surgery is a relatively common complication affecting short- and long-term survival. The renoprotective effect of vitamin D (VitD) has been confirmed in several experimental models. This study was conducted to evaluate the effect of high-dose VitD administration in patients with VitD insufficiency on the incidence of postoperative AKI, the urinary level of tubular biomarkers, and serum anti-inflammatory biomarker after coronary artery bypass graft. Design and Method: In this randomized double-blind controlled clinical trial, the patients were randomly allocated to either the VitD group (n = 50), receiving 150,000 IU VitD tablets daily for 3 consecutive days before surgery or the control group (n = 61), receiving placebo tablets. Results: There was no difference in the incidence of postoperative AKI between the groups. Both of the urinary levels of interleukin-18 and kidney injury molecule-1 were significantly increased after the operation (p < 0.001, for both). Also, the serum level of interleukin-10 was increased after 3 days of VitD supplementation (p = 0.001). In comparison with the control group, it remained on a higher level after the operation (p < 0.001) and the next day (p = 0.03). The patients with AKI had more postoperative bleeding and received more blood transfusion. Conclusion: VitD pretreatment was unable to impose any changes in the incidence of AKI and the urinary level of renal biomarkers. However, high-dose administration of VitD may improve the anti-inflammatory state before and after the operation. Further studies are needed to assess the renoprotective effect of VitD on coronary surgery patients.

Human kidney injury molecule-1 as a urine biomarker differentiating urothelial and renal cell carcinoma.

IntroductionUrine concentration of human kidney injury molecule-1 (KIM-1) is suggested to be increased in patients with renal cell carcinoma (RCC). However, it has never been tested in patients with urothelial tumors, while preoperative differentiation between RCC and upper tract urothelial carcinoma (UTUC) plays an essential role in therapeutic decisions.The aim of the study was to evaluate the role of urinary KIM-1 expression in preoperative differentiation between RCC and urothelial carcinoma (UC).Material and methodsSixty-four participants were enrolled in the study, including 30 patients with RCC and 27 with UC (16 with UTUC and 11 with bladder tumor). Preoperative urinary KIM-1 levels were measured using a commercially available ELISA kit and normalized to urinary creatinine levels.ResultsThe median concentration of urinary KIM-1 normalized to urinary creatinine was lower in patients with RCC compared to UC (1.35 vs 1.86 ng/mg creatinine, p = 0.04). The comparison between RCC and UTUC shows even more significant difference (1.33 vs 2.23 ng/mg creatinine, p = 0.02). Urinary KIM-1 concentration did not correlate with tumor stage nor grade in any of the groups. ROC analysis to identify UC revealed AUC of 0.657 with sensitivity 33.3% and specificity 96.7% at the cut-off value of 3.226 ng/mg creatinine. Among patients with eGFR ≥60 mL/min/1.73 m², ROC analysis to detect UC achieved AUC of 0.727 with sensitivity 69.5% and specificity 70.2%.ConclusionsUrine KIM-1 can potentially differentiate UC from RCC. However, a wide range of observed results and limited sensitivity and specificity requires caution in making clinical decisions before confirmatory studies.

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

Value of urinary kidney injury molecule-1 levels in predicting acute kidney injury in very low birth weight preterm infants.

ObjectiveThis study aimed to evaluate the significance of urinary kidney injury molecule-1 (uKIM-1) levels in predicting acute kidney injury (AKI) and mortality in very low birth weight (VLBW) preterm infants.MethodsThis prospective, observational cohort study was conducted on 39 VLBW preterm infants. Serum creatinine (SCr) and uKIM-1 levels were measured in the first 24 and 48 to 72 hours of life. The estimated glomerular filtration rate (eGFR) was calculated. Levels of uKIM-1 were measured with an enzyme-linked immunosorbent assay.ResultsAmong 39 VLBW infants, 9 (23%) developed AKI. The mortality rate was 17.9% (n = 7 neonates). There was no significant difference in SCr levels, uKIM-1 levels, or the eGFR obtained in the first 24 hours in the AKI group compared with controls. However, significant differences were found in SCr and uKIM-1 levels, and the eGFR rate at 48 to 72 hours between the groups. Levels of uKIM-1 were significantly higher in non-survivors than in survivors in the first 24 and 48 to 72 hours of life.ConclusionThe level of uKIM-1 can be used as a simple noninvasive diagnostic method for predicting AKI and mortality, especially within 48 to 72 hours of life.Clinical trial registration: We do not have a clinical trial registration ID. In Turkey, clinical trial registration is not required for non-drug, noninvasive, clinical studies.

ADAMTS13 inhibits oxidative stress and ameliorates progressive chronic kidney disease following ischaemia/reperfusion injury.

Reduced A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif member 13 (ADAMTS13) levels are observed in kidney disease. We test whether recombinant human ADAMTS13 (rhADAMTS13) mitigates renal injury in chronic kidney disease (CKD) and the potential mechanisms. CKD was established 3months after ischaemia/reperfusion (IR). ADAMTS13 and von Willebrand factor (vWF) levels, renal function and morphological changes were analysed. Afferent arteriolar responses to angiotensin II (Ang II) and acetylcholine (ACh) were measured. Oxidative stress-related molecules were detected. Higher vWF and lower ADAMTS13 levels were observed in CKD mice, which were markedly attenuated by rhADAMTS13. rhADAMTS13 alleviated renal dysfunction, as documented by decreased blood urea nitrogen (BUN), serum creatinine, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) levels in CKD mice. Moreover, rhADAMTS13 attenuated transforming growth factor (TGF)-β1/Smad3 activation. Plasma vWF: ADAMTS13 ratio showed positive correlations with malondialdehyde (MDA), hydrogen peroxide (H2 O2 ) and proteinuria, and correlated inversely with superoxide dismutase (SOD) and catalase (CAT). Finally, rhADAMTS13 inhibited reactive oxygen species (ROS) levels and improved microvascular functional disorders, accompanied by the inhibition of glycogen synthase kinase (GSK) 3β hyperactivity and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Acute kidney injury (AKI) reduces the expression of ADAMTS13 that contributes to progressive CKD, microvascular dysfunction, oxidative stress, inhibition of Nrf2 activity and renal histopathological damage. All of which can be alleviated by administration of rhADAMTS13.

KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p &lt;0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

Effect of preeclampsia and its severity on maternal serum NGAL and KIM-1 levels during pregnancy and the post-pregnancy period

ObjectiveThe purpose of this trial was to appraise the effects of preeclampsia and its intensity on maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels during pregnancy and the post-pregnancy period. Study designFirstly pregnant participants (n = 156) were separated into three groups, as control, mild, and severe preeclampsia. Secondly women in post-pregnancy period (n = 368) were separated into three groups according to history of pregnancy, as healthy control, mild, and severe preeclampsia. These women were identified through the hospital data system and contacted by telephone to participate in the study. ResultsOur study comprised 147 patients, 77 of whom were pregnant and 70 of whom were in their post-pregnancy period after the exclusion criteria had been applied. In terms of maternal serum NGAL levels, there is a significant increase in the severe preeclampsia group compared with that in the mild preeclampsia and normal pregnancy groups (p < 0.001). During the post-pregnancy period, the maternal serum NGAL levels were found significantly higher in the severe preeclampsia group than in the mild preeclampsia group and non-hypertension control group (p < 0.001). Maternal serum KIM-1 levels were found as significantly higher in the severe and mild preeclampsia groups than in the non-hypertension pregnancy group (p = 0.004). During the post-pregnancy period, maternal serum KIM-1 levels were found as similar among all post pregnant groups (p = 0.792). ConclusionsOur results indicated that as the severity of preeclampsia increases, kidney damage as assessed using NGAL levels continues for a long period of time, even during the post-pregnancy period.